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Responses to Laboratory Psychosocial Stress in Postpartum Women MARGARET ALTEMUS, MD, LAURA S. REDWINE, PHD, YEUNG-MEI LEONG, PHD, CHERYL A. FRYE, PHD, STEPHEN W. PORGES, PHD, AND C. SUE CARTER, PHD Objective: Lactation has been associated with attenuated hormonal responses to exercise stress in humans. This study was designed to determine the effect of lactation on hypothalamic-pituitary-adrenal axis, autonomic nervous system, and anxiety responses to psychological stress. Method: The Trier Social Stress Test was administered to 24 lactating women, 13 postpartum nonlactating women, and 14 healthy control women in the early follicular phase of the menstrual cycle. Lactating women were stressed at least 40 minutes after last feeding their infant. Results: ACTH, cortisol, heart rate, diastolic blood pressure, systolic blood pressure, and subjective anxiety ratings were all significantly increased in response to the psychological stress (all p ⬍ .0001). There were no differences among the three groups in any of these responses to the stress. However, postpartum nonlactating women did have a persistently higher systolic blood pressure and lower cardiac vagal tone than the lactating women and control subjects. In addition, the typical negative correlation between cardiac vagal tone and heart rate was consistently higher in lactating women than nonlactating postpartum women and controls, which suggests stronger vagal control of heart rate in lactating women. In addition, there was no change in oxytocin or allopregnanolone in response to the stress, and baseline oxytocin and allopregnanolone levels did not differ among the three groups. Conclusions: These results indicate that physiological and subjective responses to social stress are not attenuated in lactating women tested at least one hour after feeding their infant. However, enhanced vagal control of cardiac reactivity was observed in lactating women. In addition, postpartum women who did not lactate showed evidence of increased sympathetic and decreased parasympathetic nervous system tone. Key words: stress, lactation, oxytocin, allopregnanolone, cortisol, vagal tone.

ACTH ⫽ adrenocorticotropin; AUC ⫽ area under the curve.

Both animal and human studies indicate that lactation is characterized by reductions in stress responsivity. In rats, plasma ACTH and corticosterone (1– 4), catecholamine (5), and oxytocin (1, 6) responses to stress are all attenuated during lactation. In addition, immediate early gene responses to both pharmacologic and environmental stressors are blunted in multiple brain areas of laboratory rats (7–9). Corticotropin-releasing hormone (CRH) and enkephalin mRNA responses to hypertonic saline stress also are reduced in the hypothalamic paraventricular nucleus of lactating rats (2). There is evidence that reduced noradrenergic stimulation of the paraventricular nucleus contributes to the reduction of hypothalamic-pituitary-adrenal (HPA) axis responsivity during lactation (10, 11). In addition to lactation-associated blunting of biological

From the Department of Psychiatry, Weill Medical College, Cornell University, New York, NY (M.A.); VA San Diego Health Care System, San Diego, CA (L.S.R.); Laboratory of Clinical Science, NIMH Intramural Research Program, Bethesda, MD (Y.-M.L.); Department of Psychology, The University at Albany-SUNY, Albany, NY (C.A.F.); Department of Psychiatry (S.W.P., C.S.C.), University of Illinois, Chicago Medical School, Chicago, IL. Address correspondence to Margaret Altemus, MD, Box 244, Weill Medical College, Cornell University, 1300 York Avenue, New York, NY 10021. Email: [email protected] Received for publication May 11, 2000; revision received December 15, 2000.

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responses to stress, behavioral studies have demonstrated suppression of multiple fear behaviors in lactating rats and mice (12–17). In women, two studies have found attenuation of physiological stress responses during lactation. In response to exercise stress, lactating women, compared with postpartum nonlactating women, had reduced ACTH, cortisol, and glucose responses to stress. Lactating women in this study also had lower basal norepinephrine levels (18). In response to videotapes of their infants, lactating women had a blunted increase in heart rate compared with postpartum nonlactating women and also had reduced baseline galvanic skin conductance, a measure of sympathetic nervous system activity (19). We report here a study of autonomic nervous system, hormonal, and subjective responses to another psychological stress in breast-feeding women compared with both postpartum bottle-feeding women and nonpostpartum women. The Trier Social Stress Test was used as the stressor because it has been found in multiple studies to induce reliable physiological and psychological responses to stress (20). In this study, we were most interested in determining whether lactation was associated with suppression of central nervous system stress responsivity, independent of any effect of elevations in circulating oxytocin to suppress ACTH release at the pituitary. Intravenous infusion of oxytocin blunts HPA axis responses to a variety of stressors (21–23), and, just as endogenous oxytocin is elevated during bouts of lactation, circulating plasma cortisol and ACTH levels are reduced (24, 25). To ensure that plasma oxytocin had returned

Psychosomatic Medicine 63:814 – 821 (2001)

POSTPARTUM STRESS RESPONSES to baseline levels before onset of the stressor, postpartum women were tested at least 40 minutes after their last infant feeding. This design is similar to the design of our prior exercise stress study in lactating women, which demonstrated reduced HPA axis responses to stress in lactating women (18). SUBJECTS AND METHODS Subjects Fifty-one healthy women participated in the study after giving written, informed consent. Twenty-four lactating women, 13 postpartum nonlactating women, and 14 healthy control women participated in the study. Subjects were recruited by advertisements for paid participation in a study of pregnancy and infant feeding. All subjects were in good health as assessed by physical exam and screening laboratory tests including complete blood count, thyroid function tests, a comprehensive blood chemistry panel, and a urine toxicology screen. No subjects were taking medications other than vitamins. Subjects were 20 to 40 years of age, and mean (⫾SD) age did not differ among subject groups (bottle feeders: 31 ⫾ 5, breast feeders: 31 ⫾ 4, controls: 28 ⫾ 6 years). Postpartum women were 6 to 24 weeks postpartum, and the mean (⫾SD) number of weeks postpartum did not differ between lactating and nonlactating women (breast feeders: 11 ⫾ 4 and bottle feeders: 9 ⫾ 4 weeks). Women in the bottle-feeding group had either never lactated or had stopped lactating at least 4 weeks before participating in the study. Women in the breast-feeding group provided at least 90% of their infant’s nutrition through breast milk. Although most postpartum subjects were amenorrheic, six nonlactating and one lactating subject resumed menses before the stress interview. Control subjects had not been pregnant or lactating for at least 1 year. All control subjects had regular menstrual cycles and were tested 3 to 8 days after onset of menses.

Experimental Protocol The Trier Social Stress Test. After insertion of an indwelling venous catheter, subjects rested in a chair for one hour before the start of the Trier Social Stress Test. The stress protocol began with a 3-minute instruction period for the forthcoming task (to prepare a 5-minute speech for a job interview for a clerk position in a tire store). Subjects were told that the interview would be videotaped and scored for evidence of anxiety and effective communication. The subject then had a 7-minute anticipation/preparation period. Next, the interview began with the arrival of three evaluators. During the first 5 minutes, the subject was expected to explain why she would be a good candidate for the job, and, during the second 5 minutes, she was asked to perform a serial subtraction task. During the last 40 minutes of the 1-hour rest period, the 20minute stress procedure, and the following hour, mothers were separated from their infants. Lactating women were asked to feed their infants at the start of the 1-hour rest period to ensure that oxytocin levels would be at baseline at the start of the stress protocol and so that infants would not need to be fed during the 80-minute study period. Testing was conducted between 10 AM and 3 PM. Physiological variables. Heart rate and cardiac vagal tone were recorded continuously beginning 10 minutes before the introduction to the task. Cardiac vagal tone was quantified, via time series analyses of the beat-to-beat heart periods, as the natural logarithm of the amplitude of respiratory sinus arrhythmia (Vagal Tone Monitor, Delta Biometrics, Bethesda, MD) (26). Heart rate and vagal tone were


averaged over 10-minute periods. Blood pressure was measured every 10 minutes by an automated blood pressure recording device (Dynamap, Criticon, Tampa, FL). Heart-rate data were not obtained in one subject, cardiac vagal tone data were not obtained in four subjects, and blood pressure measures were not obtained in two subjects. Blood sampling. Baseline blood samples were obtained 10 minutes before and immediately before the introduction of the task (⫺10, 0). Blood samples were also taken at the end of the interview (⫹20) and every 10 minutes for the following hour (⫹30 to ⫹80). ACTH and cortisol were measured at every time point. Because of the short half-life of oxytocin, oxytocin was measured at baseline (⫺10) and immediately after the end of the stress interview (⫹20), which is the time of peak ACTH release in response to the stress. Allopregnanolone was measured at baseline (⫺10) and 10 minutes after termination of the stress (⫹30), because ⫹30 is the time of peak cortisol release in response to the stress interview. Subjective anxiety ratings. For ratings of subjective anxiety, desire to move, and nervousness, 100-mm Visual Analogue Scales were used. These were administered 10 minutes before the interview, immediately after the interview (⫹20), and 20 minutes after the end of the interview (⫹40). Hormone assays. Commercial radioimmunoassay kits were used to measure ACTH (Immunoradiometric assay; Nichols Diagnostics, San Juan Capistrano, CA) and cortisol (Coat-a-Count; Diagnostic Products Corp., Los Angeles, CA). The limits of detection for these kits in our laboratory are 0.3 pmol/L for ACTH and 28 nmol/L for cortisol. The intraassay coefficient of variation averaged 5% for cortisol and ACTH, and the interassay coefficient of variation was 12% for ACTH and 4% for cortisol. Estradiol and progesterone were measured by radioimmunoassay in the NIH Clinical Center Laboratory. Detection limit of the estradiol assay was 36 pmol/L. The intraassay coefficient was 5.2%, and the interassay coefficient of variation was 10% at 367 pmol/L. The detection limit of the progesterone assay was 1.3 nmol/L, and the interassay coefficient of variation was 9% at 4.1 nmol/L. Oxytocin was measured by radioimmunoassay after extraction and concentration as previously described (18). The detection limit for oxytocin was 0.67 pmol/ml. Four subjects did not have oxytocin measures. Allopregnanolone was measured by radioimmunoassay after extraction and concentration as previously described (27). The detection limit of the assay was 0.012 ng/ml, and the intraassay coefficient of variation was 9.2%. Eight subjects did not have allopregnanolone measures.

Statistical Analysis Repeated-measures analyses of variance (ANOVA) with the Greenhouse-Geiser correction was used to evaluate the effects of the stress interview and differences among the three subject groups in response to the interview. Single time-point data were compared by use of univariate ANOVA. Relationships among variables were evaluated by use of Pearson’s correlation coefficient. AUC was used for correlational analyses of multiple time-point data and was calculated by the trapezoidal method with subtraction of the baseline. The results of these correlational analyses were not corrected for multiple comparisons and should be considered to be exploratory. In addition, in order to determine possible group differences in the vagal regulation of the heart rate responses to stress, change in heart rate and cardiac vagal tone from baseline to each successive time point were correlated within each group, and the mean correlation across all six time points was compared among the three subject groups. Because the distributions of change scores were skewed, Spearman’s correlation coefficients were used for this analysis. Significance for all analyses was set at the 0.05 level.

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M. ALTEMUS et al. RESULTS Basal Measures Basal values are shown in Table 1. There were no differences among the three subject groups in the basal levels of anxiety, ACTH, cortisol, oxytocin, allopregnanolone, cardiac vagal tone, or diastolic blood pressure. There was a difference among groups in mean baseline systolic blood pressure [F(2,46) ⫽ 3.4; p ⬍ .05], with bottle feeders having higher systolic blood pressure than breast feeders and controls. There were nonsignificant trends toward lower baseline cardiac vagal tone [F(2,45) ⫽ 2.7, p ⬍ .08] and faster baseline heart rate [F(2,45) ⫽ 2.8, p ⬍ .08] in the nonlactating postpartum women and higher baseline oxytocin levels [F(2,44) ⫽ 2.3, p ⬍ .11] in breast-feeding women. Bottle-feeding women had significantly higher mean estrogen levels than breast-feeding women or controls [F(2,48) ⫽ 11.1, p ⬍ .001]. No correlation was found between the number of weeks postpartum and baseline measures of heart rate, systolic blood pressure, or cardiac vagal tone in breast-feeding or bottle-feeding women. Responses to Stress Interview Responses to the stress interview are shown in Figure 1. There was a significant increase in ACTH during the stress interview [F(8,384) ⫽ 12.6, p ⬍ .0001]. There was no main effect of subject group on ACTH and no interaction between subject group and ACTH response to the stress interview. TABLE 1.

Hormonal and physiologic responses to Trier Social Stress Test in lactating, nonlactating, and nonpostpartum women. Period of stress test (time ⫹10 to ⫹20 minutes) is represented by the shaded gray bar. Values are mean ⫾ SEM.

Basal Measures in Breast-feeding and Bottle-feeding Postpartum Women and Controls

Variable Adrenocorticotropin (pmol/ L) Cortisol (nmol/L) Estrogen (pmol/L) Progesterone (nmol/L) Oxytocin (pmol/L) Allopregnanolone (ng/ml) Heart rate (beats/min) Vagal tone Systolic pressure (mm Hg) Diastolic pressure (mm Hg) Anxiety (0–100 mm) Desire to move (0–100 mm) Nervousness (0–100 mm)

Breastfeeding Bottlefeeding

Control

3.3 ⫾ 0.2

2.8 ⫾ 0.4

3.2 ⫾ 0.4

262 ⫾ 22 121 ⫾ 17 2.4 ⫾ 1.0 1.8 ⫾ 0.1 3.8 ⫾ 0.6 69.3 ⫾ 2 7.4 ⫾ 0.2 104 ⫾ 1 65.0 ⫾ 2 13.0 ⫾ 3 15.9 ⫾ 4

240 ⫾ 28 340 ⫾ 62a 5.3 ⫾ 3.3 1.6 ⫾ 0.2 3.4 ⫾ 0.6 80.4 ⫾ 2b 6.6 ⫾ 0.3 110 ⫾ 3b 65.3 ⫾ 2 10.3 ⫾ 3 16.9 ⫾ 5

257 ⫾ 28 200 ⫾ 26 1.5 ⫾ 0.1 1.4 ⫾ 0.1 3.8 ⫾ 1.1 68.8 ⫾ 3 7.3 ⫾ 0.3 103 ⫾ 2 63 ⫾ 2 6.9 ⫾ 3 15.0 ⫾ 4

15.0 ⫾ 3

11.0 ⫾ 3

9.9 ⫾ 3

Note: Values are mean ⫾ SEM. a Bottle-feeding women ⬍ breast-feeding women and controls; p ⬍ .01. b Bottle-feeding women ⬎ breast-feeding women and controls; p ⬍ .05.

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Fig. 1.

Similarly, there was a significant increase in plasma cortisol during the stress interview [F(8,384) ⫽ 13.0, p ⬍ .0001]. Again, there was no main effect of subject group on cortisol [F(2,48) ⫽ 0.8, p ⫽ .44] and no interaction between subject group and cortisol response to the stress interview [F(16,384) ⫽ 0.2, p ⫽ .99]. Heart rate was also significantly increased in response to the stress test [F(6,282) ⫽ 23.3, p ⬍ .0001]. There was a trend toward a group effect on heart rate [F(2,47) ⫽ 2.5, p ⬍ .09] with elevated heart rate in bottle-feeding women compared with breast-feeding women and controls. There was no interaction between subject group and heart-rate response to the stress interview. There was no significant cardiac vagal tone response to the stress interview. However, there was a main effect of subject group [F(2,44) ⫽ 4.3, p ⬍ .02]. Bottle feeders had lower vagal tone compared with controls and lactating women. There was no interac-


POSTPARTUM STRESS RESPONSES tion between subject group and cardiac vagal tone response to the stress interview [F(2,264) ⫽ 1.1, p ⫽ .4]. The correlation between change in cardiac vagal tone and change in heart rate at each time point in response to stress was calculated for each group, to obtain a measure of vagal contribution to the control of heart rate. The typical negative correlation between change in cardiac vagal tone and change in heart rate was strongest in the lactating women (Table 2). The mean intra-individual Spearman’s correlation coefficient was ⫺0.68 in the lactating women, ⫺0.38 in the nonlactating postpartum women, and ⫺0.34 in the control women. There was a significant increase in diastolic pressure during the stress interview [F(9,414) ⫽ 8.4, p ⬍ .0001]. There was no main effect of subject group on diastolic blood pressure and no interaction between subject group and response to the stress interview. Systolic pressure [F(9,414) ⫽ 8.5, p ⬍ .0001] also increased significantly during the stress interview in the combined group, with a main effect of subject group [F(2,46) ⫽ 4.2, p ⬍ .02]. Bottle feeders had higher systolic pressure than the lactating and control groups. No interaction was found between subject group and response to the stress interview. Oxytocin levels did not change in response to the stress, and there was no main effect of subject group and no interaction between subject group and oxytocin response to the stress interview (Figure 2). Allopregnanolone levels did not change in response to the stress, and there was no main effect of subject group and no interaction between subject group and allopregnanolone response to the stress interview (Figure 3). During the stress interview, there was a significant increase in levels of anxiety [F(2,86) ⫽ 100.0, p ⬍ .0001], desire to move [F(2,86) ⫽ 11.5, p ⬍ .0002], and nervousness [F(2,86) ⫽ 107.0, p ⬍ .0001]. There was no main effect of subject group on these measures and no interaction between group and response to the stress interview. No significant correlations were found between TABLE 2.

Correlations of Change from Baseline in Heart Rate and Cardiac Vagal Tone

Time

Breastfeeding (n ⫽ 21)

Bottlefeeding (n ⫽ 13)

Control (n ⫽ 14)

⫹10 ⫹20 ⫹30 ⫹40 ⫹50 ⫹60

⫺.71 ⫺.67 ⫺.75 ⫺.56 ⫺.67 ⫺.74

⫺.21 ⫺.45 ⫺.36 ⫺.32 ⫺.54 ⫺.41

⫺.12 ⫺.48 ⫺.42 ⫺.47 ⫺.22 ⫺.31


Fig. 2.

Mean ⫾ SEM oxytocin levels before and immediately after the Trier Social Stress Test in lactating, nonlactating, and nonpostpartum women.

Fig. 3.

Mean ⫾ SEM allopregnanolone levels before and 10 minutes after completion of the Trier Social Stress Test in lactating, nonlactating, and nonpostpartum women.

plasma estrogen, progesterone, or oxytocin levels and AUC for ACTH, cortisol, heart rate, cardiac vagal tone, systolic blood pressure, and diastolic blood pressure within the combined group of subjects. There was a modest negative correlation between baseline oxytocin levels and baseline cardiac vagal tone (N ⫽ 45, r ⫽ ⫺.41, p ⬍ .01). There also were the expected positive correlations between AUC for ACTH and cortisol (N ⫽ 51, r ⫽ .69, p ⬍ .01) and between AUC for systolic and diastolic blood pressure (N ⫽ 49, r ⫽ .45, p ⬍ .01) and the expected negative correlation between AUC heart rate and AUC cardiac vagal tone (N ⫽ 48, r ⫽ ⫺.52, p ⬍ .01). There were no other significant correlations among AUC (or post-/prestress change scores in the case of oxytocin and allopregnanolone) for any variables.

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M. ALTEMUS et al. DISCUSSION As expected, the Trier Social Stress Test caused a significant increase in anxiety ratings, ACTH, cortisol, heart rate, diastolic blood pressure, and systolic blood pressure. However, there was no attenuation of these responses in lactating women. Instead, there was a persistently higher systolic blood pressure, increased baseline heart rate, and lower vagal tone in bottlefeeding postpartum women, compared with lactating women and non–postpartum control subjects. Although postpartum women seemed to not show the typical drop in vagal tone in response to stress, this difference from control subjects was not statistically significant. Overall, these results highlight the importance of including a non–postpartum control group in studies of lactating women and suggest that women who do not lactate postpartum have an increase in resting sympathetic nervous system tone and a decrease in parasympathetic nervous system activity. Our findings are consistent with prior reports of elevated resting norepinephrine levels (18) and skin conductance (19) in postpartum bottle-feeding women compared with postpartum women who were lactating. However, similar cortisol, ACTH, and heart rate responses to the Trier Social Stress Test in lactating and nonlactating women in the current study contrast with prior reports of decreased ACTH and cortisol responses to exercise stress (18) and attenuated heartrate responses to infant videotapes (19) in lactating compared with nonlactating women. One factor that may contribute to the differences between this psychological stress study and our prior exercise stress study is the quality or severity of the stress. There is evidence that the suppressive effects of lactation on responses to psychosocial stressors may be more transient than the suppression of responses to physical or pharmacological stressors. In rats, suppression of hypothalamic CRH mRNA responses to hypertonic saline stress are not reversed until several days after litter removal (2), but suppression of submissive behavior toward intruders reverses within 4 hours of litter removal (15). A preliminary report of another study of lactating women who were administered the Trier Social Stress test found that lactating women who fed their infants 15 minutes before onset of the Trier Social Stress Test had a reduced cortisol response, compared with lactating women who did not feed their infants before the stress interview (28). A much more transient suppression of HPA axis responses to stress in lactating women compared with lactating rats may be related to species differences in regulation of the HPA axis by circulating oxytocin. In rats, circulating oxytocin stimulates ACTH release at the pituitary. In hu-

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mans, both experimental and observational studies demonstrate reduced HPA axis reactivity when plasma oxytocin levels are elevated (21–23), which suggests that oxytocin released during a lactation bout in humans may provide time-limited suppression of HPA axis responses to psychological stress. Finally, it is also possible that, because responses to the psychosocial stress are influenced by a variety of factors, including temperament, trait anxiety, and social support (29 –32), an effect of lactation may have been obscured in this study. Although we did not find an attenuation of stress responsivity in the lactating women, we did find increased vagal control of heart rate in the lactating women compared with both postpartum nonlactating women and control subjects. Heart-rate regulation is a complex feedback system that involves both parasympathetic and sympathetic nervous system inputs. Parasympathetic control of heart rate is relayed through cardiac branches of the vagus nerve. The vagus acts as a “brake” on the intrinsic rate of the heart (33) and opposes sympathetic activity at the sinoatrial note (34). Because a respiratory rhythm originates from source nucleus of the myelinated vagus (35), the functional impact of these vagal pathways on the sinoatrial node is to produce a respiratory rhythm in the heart rate pattern. The amplitude of these rhythmic increases and decreases in heart rate at frequencies within the range of breathing (ie, respiratory sinus arrhythmia) is, thus, a valid indicator of cardiac vagal tone. Thus, cardiac vagal tone can be quantified by applying times-series analyses to measure the amplitude respiratory sinus arrhythmia (26, 36). Although, when presented as group data, the heart-rate response to the stress appears to be smooth, individual responses were quite variable because of responses to a variety of idiosyncratic internal and external stimuli. Within the lactating group, changes from baseline in vagal tone at each time point were more closely related to heart-rate changes from baseline at each time point, despite the apparent lack of typical vagal withdrawal during the actual interview stress in the postpartum groups. Future work is needed to determine whether the activity of vagal efferents to other target tissues is enhanced during lactation. Vagal efferents to the heart communicate directly, via neuroanatomically pathways, to the medullary areas that regulate smooth muscles involved in expression of emotion, which, like cardiac reactivity, may play a role in regulation of emotions and social interactions (37). Because of the cross-sectional design of this study, we are unable to determine whether the increased systolic blood pressure and heart rate and decreased cardiac vagal tone in the bottle-feeding women is a


POSTPARTUM STRESS RESPONSES trait or whether these findings are transient and will resolve with time. It is possible that temperament or environmental factors that promote higher sympathetic and lower parasympathetic tone could also predispose women to choose to bottle feed rather than breast feed their infants. Personality differences have been identified between women who choose to breast feed and those who choose to bottle feed (38 – 40). Another interpretation of the data are that, during the postpartum period, evolutionarily determined adaptive or homeostatic mechanisms come into play that are designed to incorporate the physiological changes associated with lactation. The decision not to lactate postpartum may then result in a relative increase in sympathetic nervous system activity and a decrease in cardiac vagal tone. Future studies that track blood pressure longitudinally throughout the first year postpartum or that measure autonomic function before pregnancy as well as postpartum will help to resolve this question. Although there was a small increase in estrogen levels in bottle-feeding women compared with the other two groups, it is unlikely that the increased estrogen levels contributed to the increased heart rate and blood pressure and decreased vagal tone in the bottle-feeding group. All three groups had estrogen levels at the low end of the physiological range, and estrogen levels did not correlate with any of the autonomic or HPA axis measures. In addition, estrogen treatment in postmenopausal women has been associated with reductions in blood pressure responses to stress but no change in resting blood pressure or heart rate (41, 42). Although there have been several reports of decreased anxiety in breast-feeding compared with bottle-feeding mothers (43– 47) and multiple reports of decreased expression of fear behaviors in lactating rats (12–17), there was no difference among the three groups of subjects in the current study in baseline anxiety or anxiety responses to the laboratory stress. The difference between our results and prior reports may be due to our use of only three visual analogue scales containing one-word descriptions of anxiety. As expected, given the short half-life of oxytocin and at least the 40-minute-long waiting period between the most recent breast-feeding episode and the baseline blood draw, there was no difference in baseline oxytocin levels among the three groups. However, peripheral administration of oxytocin to rats causes long-lasting reductions in blood pressure (48, 49), which suggests that lactation may contribute to the relatively decreased blood pressure in lactating compared with nonlactating mothers, despite similar oxytocin levels at the start of the laboratory stress proce-


dure. There was no increase in plasma oxytocin in response to the Trier Social Stress Test. It is possible that our ability to detect an oxytocin response to the psychological stress in our female subjects was limited by only obtaining one poststress measure of oxytocin, but our finding is consistent with reports of no reliable oxytocin response to severe exercise stress (18), noise stress (50), or negative mood induction (51) in healthy women. These observations of no oxytocin response to exercise and psychological stress in women contrast with findings in rats of robust plasma oxytocin responses to a variety of stressors (1, 6). We also measured allopregnanolone, an adrenal steroid with anxiolytic properties, which is released into the circulation in response to relatively high, acute doses of exogenous ACTH (52). Although plasma allopregnanolone is increased in response to a variety of acute stressors in rats (53), there was no increase in allopregnanolone in this group of human subjects in response to the Trier Social Stress Test. This finding suggests that the threshold for stress-induced secretion of allopregnanolone in humans in higher than the threshold for cortisol release. The lack of differences between groups in allopregnanolone levels at baseline is congruous with our finding that there were no baseline differences in serum progesterone, the precursor to allopregnanolone. In summary, lactating women did not have attenuated physiological or subjective anxiety responses to a laboratory psychosocial stress administered one hour after their last episode of lactation. However, lactating women had increased vagal contribution to heart-rate regulation, and postpartum women who were not lactating had evidence of elevated sympathetic and decreased parasympathetic nervous system activity. Longitudinal studies with more extensive personality assessments are needed to determine whether these differences in autonomic nervous system activity in postpartum women are trait-related or are a consequence of the chosen method of infant feeding. This work was performed at the Laboratory of Clinical Science in the NIMH Intramural Research Program and was also partially supported by Department of Defense Women’s Health Program Grant DAMD17-95 1-5069 and NIMH K05-MH 01050 to C.S.C. and a Dewitt Wallace Reader’s Digest Fund grant to M.A. We wish to thank Dennis Murphy, MD, for his advice and support and Jessica Zonana for her help with manuscript preparation. REFERENCES 1. Neumann ID, Torner L, Wigger A. Brain oxytocin: differential inhibition of neuroendocrine stress responses and anxiety-

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